Summary This Training Program provides graduate students with advanced education in the principles and practice of macromolecular chemistry, mechanism, and structure. All aspects of the program - formal course curriculum, laboratory rotations, informal specialized area-interest seminars, and intensive research in laboratories operating on the edge of discovery - are aimed at the question: how do biological macromolecules work? How do proteins, membranes, nucleic acids, and high-order complexes of these huge molecules use physical-chemical and structural principles to act in the enormous variety of contexts that underlie biological function? The Training Program provides support for selected graduate students in two of the four life-science graduate Ph.D. programs at Brandeis: Biochemistry, and Biophysics & Structural Biology. The former of these is a more structured program that attracts students mainly with strong academic backgrounds in chemistry and biochemistry backgrounds, while the latter is a more flexible program designed for students who have strong quantitative backgrounds but who may have weaker prior training experience in biological chemistry. Our intention is to bring these two groups of students to the same end-point and to prepare them for careers in basic research. Currently, 28 students (which will rise to 33 students in September 08) are enrolled in these two Ph.D. programs; the Training Program includes 20 participating faculty (in four departments) working in the following areas: macromolecular structure determination by x-ray crystallography and NMR, mechanistic enzymology, membrane transport and ion channel mechanisms, single-molecule analysis, high-resolution mass spectroscopy and proteomics, computational biophysics. RELEVANCE: A general rationale for the value of this program is the conviction that human disease must ultimately be understood in terms of the chemistry and physics of biological macromolecules.